2,5-dichlorophenylthioglycolic acid derivative and method for its production

ABSTRACT

The present invention is directed to novel 2,5-dichlorophenylthioglycolic acid derivative, a process for their production and a process for producing the desired product 2,5-dichlorophenylthioglycolic acid derived from said novel compounds. 2,5-dichlorophenylthioglycolic acid derivative of the present invention can be obtained by reacting 2,4,5-trichlorobenzensulfonates and thioglycolic acid in the presence of base, and said desired product can be obtained by desulfonating said compound in an aqueous solution of mineral acid. Novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates of the present invention can be used advantageously as an intermediate for the production of 2,5-dichlorophenylthioglycolic acid. The use of said intermediate makes it possible to obtain the desired product in a decreased process steps with high yield. In addition, it poses no problem of environmental pollution as pointed out with conventional methods because it uses no heavy metals.

This application is a divisional of copending application Ser. No.07/824,313, filed on Jan. 23, 1992,now U.S. Pat. No. 5,210,287, theentire contents of which are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to 2,5-dichlorophenylthioglycolic acidderivatives. More specifically, the invention relates to novel compoundof 4-carboxymethylthio-2,5-dichlorobenzenesulfonates, methods for theirproduction, and a method for producing 2,5-dichlorophenylthioglycolicacid derived from said novel compound.

2,5-dichlorophenylthioglycolic acid is a compound which is useful as anintermediate for thioindigo pigments, chemicals for the electronicindustry, pharmaceuticals and agricultural chemicals Particularly,4,4',7,7'-tetrachlorothioindigo derived from said compound is widelyused as a pigment due to its high color fastness.

BACKGROUND OF THE INVENTION

There are some conventional methods for producing2,5-dichlorophenylthioglycolic acid, including the following:

(a) the method in which 1,4-dichlorobenzene is sulfochlorinated withchlorosulfonic acid and then reduced to 2,5-dichlorothiophenol with zincpowder under acidic conditions, followed by reaction withmonochloroacetic acid to yield 2,5-dichlorophenylthioglycolic acid (U.S.Pat. No. 3440288),

(b) the method in which 2,5-dichloroaniline is diazotized and thenreacted with thiourea in the presence of copper sulfate and subsequentlyhydrolyzed to 2,5-dichlorothiophenol, followed by reaction withmonochloroacetic acid to yield 2,5-dichlorophenylthioglycolic acid (Ger.Offen. DE3715508),

(c) the method in which 1,2,4-trichlorobenzene and sodium hydrosulfideare reacted in the presence of copper acetate catalyst in liquid ammoniasolvent under increased pressure to yield 2,5-dichlorothiophenol,followed by reaction with monochloroacetic acid to yield2,5-dichlorophenylthioglycolic acid [Kogyo Kagaku, 70, 1384 (1967)].

However, these known methods respectively have the following drawbacks.

In the method of (a) above, a large amount of waste effluent whichcontains harmful heavy metals poses a major problem of environmentalpollution. In the method of (b) above, the copper compound used isdifficult to dispose of as in (a) and the production efficiency is low;it is not an economic method of production. In the method of (c) above,liquid ammonia is difficult to handle and the copper compound used isdifficult to dispose of, and additionally special equipment is requiredbecause the reaction is carried out under high pressure. Also, there isa problem of very low yield.

As stated above, all these known methods have various drawbacks and arenot industrially advantageous,

For this reason, attempts have been made to develop an industriallyadvantageous method for producing 2,5-dichlorophenylthioglycolic acid,but there is no satisfactory method.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a method forproducing 2,5-dichlorophenylthioglycolic acid easily and economicallyusing no harmful heavy metals.

It is another object of the present invention to provide a novelintermediate which serves well for the production of2,5-dichlorophenylthioglycolic acid.

It is still another object of the present invention to provide a methodfor producing the intermediate.

Accordingly, the inventors found that the desired product2,5-dichlorophenylthioglycolic acid can be prepared by reacting2,4,5-trichlorobenzenesulfonates and thioglycolic acid in the presenceof a base (Process A) to yield a novel4-carboxymethylthio-2,5-dichlorobenzenesulfonate represented by formula(I), and desulfonating it using an aqueous solution of mineral acid(Process B). The inventors made further investigations based on thisfinding, and developed the present invention.

Accordingly, the present invention essentially relates to:

(1) novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates,

(2) a method for producing novel4-carboxymethylthio-2,5dichlorobenzenesulfonates characterized byreacting 2,4,5trichlorobenzenesulfonates and thioglycolic acid in thepresence of a base,

(3) a method for producing 2,5-dichlorophenylthioglycolic acidcharacterized by desulfonating4-carboxymethylthio-2,5dichlorobenzenesulfonates using an aqueoussolution of mineral acid, and

(4) a method for producing 2,5-dichlorophenylthioglycolic acidcharacterized by reacting 2,4,5-trichlorobenzenesulfonates andthioglycolic acid in the presence of a base and subsequently reactingthe reaction mixture with mineral acid or an aqueous solution of mineralacid.

The method for producing 2,5-dichlorophenylthioglycolic acid accordingto the present invention is a totally novel method and is characterizedin that:

(1) the use of 2,4,5-trichlorobenzenesulfonates as a starting materialoffers improvement in the reactivity of the 4-position chlorine atom dueto the strong electron attracting property of the sulfone group and thusmakes reaction with thioglycolic acid in the presence of base easy andpermits direct introduction of thioglycol group (Process A), and##STR1## (wherein M represents hydrogen, sodium or potassium) (2) thenovel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates thus obtained,which are 2,5-dichlorophenylthioglycolic acid derivatives, can easily bedesulfonated to the desired 2,5-dichlorophenylthioglycolic acid byreacting with an aqueous solution of mineral acid due to the action ofthioglycol group, which is an electron donor (Process B). The reactionproceeds with high yield in both processes.

In the of above-mentioned Process A, the2,4,5-trichlorobenzenesulfonates used, as the starting material are2,4,,5-trichlorobenzenesulfonic acid or, alkali metal salt thereof suchas sodium, potassium or others of said sulfonic acid. ##STR2## (whereinM represents hydrogen, sodium or potassium)

As stated above, the method of the present invention is a unique methodutilizing the chemical nature of sulfone group and can be said to beboth economically and industrially advantageous because the number ofprocess steps are decreased and it gives a high yield of the desiredproduct, 2,5-dichlorophenylthioglycolic acid. In addition, the method ofthe present invention is free of environmental pollution problemsbecause it uses no heavy metals.

DETAILED DESCRIPTION OF THE INVENTION

2,4,5-trichlorobenzenesulfonates, the starting materials for the presentinvention, can easily be obtained by a known method, for example, bysulfonating 1,2,-trichlorobenzene. The reaction mixture obtained throughthe above sulfonation process can be used in Process A for the presentinvention.

Specifically, Process A is a process in which2,4,5-trichlorobenzenesulfonates are reacted with thioglycolic acid inthe presence of a base to yield novel4-carboxymethylthio-2,5-dichlorobenzenesulfonates, which are derivativesof 2,5-dichlorophenylthioglycolic acid, with high yield.

Examples of bases include hydroxides of alkali metal, such as sodiumhydroxide and potassium hydroxide, carbonates of alkali metal such assodium carbonate and potassium carbonate and alcoholates of alkalimetal, such as sodium methylate and sodium ethylate, with preferencegiven to sodium hydroxide because it is less expensive.

When using sodium salt as the base, sodium4-carboxymethylthio-2,5-dichlorobenzenesulfonate is obtained. When usingpotassium salt as the base, potassium4-carboxymethylthio-2,5-dichlorobenzenesulfonate is obtained. Acidifyingsaid obtained sodium salt or potassium salt by ion-exchange methodyields 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid as shownbelow. ##STR3## When using alkali metal salts of2,4,5-trichlorobenzenesulfonic acid as the starting material, the samekind of alkali metal salt is preferably used as the base.

The amount of base used is normally in the range of 2.0 to 6.0 mol,preferably 3.0 to 5.5 mol per mol of 2,4,5-trichlorobenzenesulfonates.If the amount of base is less than 2.0 mol, the yield of the desired4-carboxymethylthio-2,5-dichlorobenzenesulfonates decreases; if theamount of base used is more than 6.0 mol, no corresponding increase inyield is obtained so that it is economically disadvantageous.

The amount of thioglycolic acid used is normally in the range from 0.9to 2.0 mol, preferably 1.0 to 1.5 mol per mol of2,4,5-trichlorobenzenesulfonates. If the amount of thioglycolic acid isless than 0.9 mol, the yield of the desired4-carboxymethylthio-2,5-dichlorobenzenesulfonates decreases; if theamount exceeds 2.0 mol, no corresponding increase in yield is obtainedso that it is economically disadvantageous.

The reaction solvent used is not subject to limitation. Examples ofreaction solvents which can be used for the present invention includewater, alcohols such as methanol, ethanol, propanol, butanol andethylene glycol, polar solvents such as N,N-dimethylformamide,N-methyl-2-pyrrolidone, dimethylsulfoxide and sulfolane and mixturesthereof, with preference given to water because it is economic.

Reaction temperature are is normally in the range from 70° to 250° C.,preferably 90° to 180° C. Temperatures exceeding 250° C. results in areduction in the yield of4-carboxymethythio-2,5-dichlorobenzenesulfonates due to side reactions;when the reaction temperature is under 70° C., the reaction velocityobtained is too low for practical use.

The reaction proceeds under a normal pressure of 1 kg/cm² (hereinafterall figures for pressure are shown in absolute unit). In this case, areaction time of 10 to 90 hours is required. When the reaction iscarried out under increased pressure at increased temperature, thereaction time can be shortened. The pressure is normally under 20kg/cm², preferably between 2 and 10 kg/cm². Under increased pressuresexceeding 20 kg/cm², the reaction velocity is too high to control;therefore, such high pressures are undesirable from the viewpoint ofoperability.

Consequently, the reaction can be completed in any reaction time byselecting appropriate reaction pressure and temperature within theabove-mentioned ranges, as described in the examples given below.

The 4-carboxymethylthio-2,5-dichlorobenzenesulfonates thus obtained canbe isolated by an appropriately selected known means, such as filtrationor extraction under acidic conditions.

The desired product 2,5-dichlorophenylthioglycotic acid can be obtainedby heating and desulfonating the4-carboxymethylthio-2,5-dichlorobenzenesulfonates obtained inaforementioned Process A in an aqueous solution of mineral acid (ProcessB).

Examples of the aqueous solution of mineral acid used in Process Binclude aqueous solutions of sulfuric acid, those of hydrochloric acidand those of phosphoric acid, with preference given to those of sulfuricacid. Although the concentration of the aqueous solution of mineral acidfor the desulfonation varies depending on the type of the mineral acid,good results are obtained when the concentration is in the range of from30 to 80%. Concentrations lower than 30% or higher than 80% areundesirable; if the concentration of the aqueous solution of mineralacid is lower than 30%, the reaction velocity is too low for practicaluse; if it exceeds 80%, the yield of the desired product2,9-dichlorophenylthioglycolic acid decreases due to side reactions.

The amount of mineral acid used is normally in the range from 0.09 to 50mol, preferably 0.1 to 30 mol per mol of4-carboxymethylthio-2,-dichlorobenzenesulfonates. Amounts lower than0.05 mol or higher than 50 mol are undesirable; if the amount is lessthan 0.05 mol, the reaction rate is too low; if the amount exceeds 50mol, no corresponding reaction rate increase is obtained, and the amountof mineral acid to be disposed of increases.

Reaction temperatures for Process B are normally in the range from 100°to 200° C., preferably 120° to 160° C. Reaction temperatures exceeding200° C. result in a reduction in the yield of the desired product2,5-dichlorophenylthioglycolic acid, due to side reactions; if thereaction temperature is lower than 100° C., the reaction rate obtainedis too low for practical use.

Process B requires no solvent, and an aqueous solution of mineral acidcan be used as a solvent. When the amount of mineral acid is low, asolvent may be added. If used the solvent, type is not subject tolimitation, as long as it is inert in the desulfonation reaction.Examples of such solvents include halogenated aromatic compounds, suchas chlorobenzene, dichlorobenzene and trichlorobenzene, ethylene glycolderivatives such as diethylene glycol dimethyl ether and polar solvents,such as sulfolane.

The production of 2,9-dichlorophenylthioglycolic acid is carried out inProcess B after isolating the4-carboxymethylthio-2,5-dichlorobenzenesulfonates obtained in Process A,as stated above. In Process A, the4-carboxymethylthio-2,5-dichlorobenzenesulfonates may also be usedwithout isolation; mineral acid or an aqueous solution of mineral acidis added to the reaction mixture of Process A, followed by adesulfonation reaction in the next process (Process B). It is thereforepossible to produce 2,5-dichlorophenylthioglycolic acid in a one-potreaction. In this case, the amount of mineral acid used, reactionconditions and other factors are the same as above.

The 2,5-dichlorophenylthioglycolic acid thus obtained can easily beseparated, by diluting the reaction mixture with water and thenfiltering it.

As stated above, according to the present invention, the desired product2,5-dichlorophenylthioglycolic acid can easily be obtained bydesulfonating in an aqueous solution of mineral acid the novel4-carboxymethylthio-2,5-dichlorobenzenesulfonates, which are derivativesof 2,5-dichlorophenylthioglycolic acid obtained by reacting2,4,5-trichlorobenzenesulfonates and thioglycolic acid in the presenceof a base.

The novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates can be usedadvantageously as an intermediate for the production of2,5-dichlorophenylthioglycolic acid. The use of said intermediate makesit possible to obtain the desired product 2,5-dichlorophenylthioglycolicacid with fewer process steps and high yields. The method of the presentinvention is thus both economically and industrially advantageous andposes no problem of environmental pollution as pointed out withconventional methods because it uses no heavy metals.

EXAMPLES

The present invention is hereinafter described in more detail by meansof the following working examples, but the invention is not limited bythese examples.

Example 1

To a 300 ml three-necked flask equipped with a stirrer, a thermometerand a condenser were charged 26.15 g (0.100 mol) of2,4,5-trichlorobenzenesulfonic acid, 9.66 g (0.105 mol) of thioglycolicacid, 12.6 g (0.315 mol) of sodium hydroxide and 200 ml of water,followed by stirring at 100° C. for 10 hours. Then, after cooling toroom temperature, the insoluble substances were filtered out. Then, thefiltrate was acidified with concentrated hydrochloric acid. Theresulting crystal was collected by filtration to yield 23.8 g of a crudecrystal. This crude crystal was dissolved in methanol. After separationfrom the side product inorganic salts, the crystal was purified to yield23.7 g of a white powder, which was identified as sodium4-carboxymethylthio-2,5-dichlorobenzenesulfonate from the physicalproperty data shown below. Its yield relative to2,4,5-trichlorobenzenesulfonic acid was 70.0%.

The melting point, elemental analysis data, NMR spectrum data and IRspectrum data of sodium 4-carboxymethylthio-2,5dichlorobenzenesulfonateare shown below.

melting point: more than 300° C.

    ______________________________________                                        elemental analysis                                                                        C       H       Cl    S      Na                                   ______________________________________                                        found       28.4%   1.5%    20.8% 18.7%  6.7%                                 calculated  28.3%   1.5%    20.9% 18.9%  6.8%                                 ______________________________________                                    

NMR(δppm, CD₃ OD): 7.98(S, 1H), 7.46(S, 1H), 3.98(S, 2H) IR(cm⁻¹, KBr):3500, 3000, 1730, 1220, 1190

Example 2

25.7 g of white powder was obtained in the same manner as in Example 1except that the sodium hydroxide was replaced with 17.6 g (0.315 mol) ofpotassium hydroxide, followed by separation and purification. The whitepowder thus obtained was identified as potassium4-carboxymethylthio-2,5-dichlorobenzenesulfonate from the physicalproperty data shown below. The yield relative to2,4,5-trichlorobenzenesulfonic acid was 72.5%.

melting point: more than 300° C.

    ______________________________________                                        elemental analysis                                                                        C        H       Cl    S     K                                    ______________________________________                                        found       27.2%    1.5%    19.9% 17.8% 10.8%                                calculated  27.0%    1.4%    20.0% 18.0% 11.0%                                ______________________________________                                    

NMR(δppm, CD₃ OD): 7.98(S, 1H), 7.46 (S, 1H), 3.98(S, 2H) IR(cm⁻¹, KBr:)3500, 3000, 1730, 1220, 1190

Example 3

10.0 g of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonateobtained in Example 1 was acidified by cation exchange resin. Afterseparation and purification, 8.2 g of white powder was obtained. Thewhite powder thus obtained was identified as4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid from the physicalproperty data shown below.

melting point: more than 300° C.

    ______________________________________                                        elemental analysis                                                                          C       H        Cl    S                                        ______________________________________                                        found         30.4%   1.9%     22.1% 20.0%                                    calculated    30.3%   1.9%     22.4% 20.2%                                    ______________________________________                                    

NMR(δppm, CD₃ OD): 7.98(S, 1H), 7.46(S, 1H), 3.98(S,2H) IR(cm⁻¹, KBr):3500, 3000, 1730, 1220, 1190

Example 4

To a 300 ml autoclave equipped with a stirrer and a thermometer werecharged 12.6 g (0.315 mol) of sodium hydroxide and 200 ml of water,followed by addition of 26.15 g (0.100 mol) of2,4,5-trichlorobenzenesulfonic acid and 9.66 g (0.105 mol) ofthioglycolic acid and stirring at 150° C. under hermetic conditions for6 hours. Through the reaction time pressure showed 5.0 kg/cm². Aftercompletion of the reaction, the reaction mixture was cooled to roomtemperature and then assayed by high performance liquid chromatography;it was found that 33.3 g of sodium4-carboxymethylthio-2,5-dichlorobenzenesulfonate was produced. Thereaction production ratio was 98.1% relative to2,4,5-trichlorobenzenesulfonic acid.

Examples 5 through 8

Sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was obtained inthe same manner as in Example 4 a except that reaction was carried outusing the reaction pressures, reaction temperatures and reaction timesshown in Table 1. The results are shown in Table 1

                  TABLE 1                                                         ______________________________________                                                                         production ratio of                                                           sodium 4-carboxy-                                  reaction reaction   reaction                                                                             methylthio-2,5-                              Exam. pressure temperature                                                                              time   dichloro-                                    No.   (kg/cm.sup.2)                                                                          (°C.)                                                                             (Hr)   benzenesulfonate                             ______________________________________                                        5      1       100        15     83.6                                         6      2       120        6      84.7                                         7     10       170        1.5    98.0                                         8     14       180        0.8    97.8                                         ______________________________________                                    

Example 9

To a 300 ml three-necked flask equipped with a stirrer, a thermometerand a condenser were charged 33.9 g (0.10 mol) of sodium4-carboxymethylthio-2,5-dichlorobenzenesulfonate obtained in Example 1and 200 g(1.22 mol) of 60% sulfuric acid, followed by stirring at 140°to 145° C. for 10 hours. Then, after cooling to room temperature, thereaction mixture was diluted with water and then filtered, washed withwater and dried to yield 22.2 g of a white powder of2,5-dichlorophenylthioglycolic acid. Its yield relative to sodium4-carboxymethylthio-2,5-dichlorobenzenesulfonate was 93.6%.

Example 10

Using the same procedure as in Example 9 except that the amount of 60%sulfuric acid was changed to 90 g (0.55 mol), 21.8 g of2,5-dichlorophenylthioglycolic acid was obtained. Its yield relative tosodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was 92.0%.

Example 11

22.1 g of the white powder, 2,5-dichlorophenylthioglycolic acid wasobtained in the same manner as in Example 9 except that 31.7 g (0.10mol) of 4-carboxymethylthio-2,5dichlorobenzenesulfonic acid obtained inExample 3 was used. Its yield relative to4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid was 93.2%.

Example 12

To the reaction mixture obtained in Example 4 was added 80 g (0.80 mol)of 98% concentrate sulfuric acid with stirring, followed by heating to140° to 145° C. During this process, 150 g of water was distilled off.Stirring was continued for 10 more hours at this temperature. Then,after cooling to room temperature, the reaction mixture was diluted withwater and then filtered, washed with water and dried to yield 21.1 g ofa white powder of 2,5-dichlorophenylthioglycolic acid. Its yieldrelative to 2,4,5-trichlorobenzenesulfonic acid was 89.0%.

What is claimed is:
 1. A process for producing2,5-dichlorophenylthioglycolic acid which comprises the steps of:(a)reacting 2,4,5-trichlorobenzenesulfonates represented by the formula:##STR4## wherein M represents hydrogen, sodium or potassium, andthioglycolic acid in the presence of base; and (b). reacting thereaction mixture obtained in the step (a) with mineral acid or anaqueous solution of mineral acid.
 2. A process according to claim 1wherein said base is sodium hydroxide.
 3. A process according to claim 1wherein said base is potassium hydroxide.
 4. A process according toclaim 1 wherein the amount of said base used is 2.0 to 6.0 mol per molof 2,4,5-trichlorobenzenesulfonates.
 5. A process according to claim 1wherein the reaction of step (a) proceeds under the pressure of not morethan 20 kg/cm².
 6. A process according to claim 1 wherein said aqueoussolution of mineral acid is aqueous sulfate solution.
 7. A processaccording to claim 1 wherein the amount of said aqueous solution ofmineral acid used is 0.05 to 50 mol per mol of4-carboxymethylthio-2,5-dichlorobenzenesulfonates.
 8. A processaccording to claim 1 wherein the reaction of step (a) proceeds at atemperature from 70°-250° C. and the reaction proceeds at a pressurefrom 2-10 kg/cm².
 9. A process according to claim 8 wherein the reactionproceeds at a temperature from 90°-180° C.
 10. A process according toclaim 1 wherein the amount of said thioglycolic acid used is 0.9 to 2.0mole per mole of 2,4,5-trichlorobenzenesulfonates.
 11. A processaccording to claim 4 wherein the amount of said base used is 3.0 to 5.5moles per mole of 2,4,5-trichlorobenzenesulfonates.
 12. A processaccording to claim 1 wherein the reaction of step (b) proceeds at atemperature from 100°-200° C.
 13. A process according to claim 12wherein the reaction proceeds at a temperature from 120°-160° C.2